Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain
| Autor: | Martha S. Windrem, Neeta S. Roy, Robert A Goodman, Marta Nunes, Steven A. Goldman, Guy M. McKhann, William K. Rashbaum, Theodore H. Schwartz |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
General Biochemistry Genetics and Molecular Biology White matter Mice Myelin Fetus medicine Animals Humans Microscopy Confocal biology Stem Cells Myelin Basic Protein General Medicine Cell sorting Immunohistochemistry Oligodendrocyte Myelin basic protein Cell biology Microscopy Electron Oligodendroglia stomatognathic diseases medicine.anatomical_structure nervous system Forebrain Immunology biology.protein Neural cell adhesion molecule Demyelinating Diseases |
| Zdroj: | Nature Medicine. 10:93-97 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Both late-gestation and adult human forebrain contain large numbers of oligodendrocyte progenitor cells (OPCs). These cells may be identified by their A2B5(+)PSA-NCAM(-) phenotype (positive for the early oligodendrocyte marker A2B5 and negative for the polysialylated neural cell adhesion molecule). We used dual-color fluorescence-activated cell sorting (FACS) to extract OPCs from 21- to 23-week-old fetal human forebrain, and A2B5 selection to extract these cells from adult white matter. When xenografted to the forebrains of newborn shiverer mice, fetal OPCs dispersed throughout the white matter and developed into oligodendrocytes and astrocytes. By 12 weeks, the host brains showed extensive myelin production, compaction and axonal myelination. Isolates of OPCs derived from adult human white matter also myelinated shiverer mouse brain, but much more rapidly than their fetal counterparts, achieving widespread and dense myelin basic protein (MBP) expression by 4 weeks after grafting. Adult OPCs generated oligodendrocytes more efficiently than fetal OPCs, and ensheathed more host axons per donor cell than fetal cells. Both fetal and adult OPC phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets. |
| Databáze: | OpenAIRE |
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